Role of nitric oxide in the development and partial reversal of allergen‐induced airway hyperreactivity in conscious, unrestrained guinea‐pigs
M Schuiling, AB Zuidhof, MAA Bonouvrie… - British journal of …, 1998 - Wiley Online Library
M Schuiling, AB Zuidhof, MAA Bonouvrie, N Venema, J Zaagsma, H Meurs
British journal of pharmacology, 1998•Wiley Online LibraryUsing a conscious, unrestrained guinea‐pig model of allergic asthma, we investigated the
role of endogenous nitric oxide (NO) in the regulation of airway (hyper) reactivity to
histamine before and after the allergen‐induced early and late asthmatic reactions, by
examining the effect of inhalation of the NO synthase inhibitor Nω‐nitro‐l‐arginine methyl
ester (l‐NAME, 12 mm, 15 min) on the histamine‐induced airway obstruction of ovalbumin‐
sensitized guinea‐pigs before, and at 5.5 h and 23.5 h after allergen challenge. Before …
role of endogenous nitric oxide (NO) in the regulation of airway (hyper) reactivity to
histamine before and after the allergen‐induced early and late asthmatic reactions, by
examining the effect of inhalation of the NO synthase inhibitor Nω‐nitro‐l‐arginine methyl
ester (l‐NAME, 12 mm, 15 min) on the histamine‐induced airway obstruction of ovalbumin‐
sensitized guinea‐pigs before, and at 5.5 h and 23.5 h after allergen challenge. Before …
- Using a conscious, unrestrained guinea‐pig model of allergic asthma, we investigated the role of endogenous nitric oxide (NO) in the regulation of airway (hyper)reactivity to histamine before and after the allergen‐induced early and late asthmatic reactions, by examining the effect of inhalation of the NO synthase inhibitor Nω‐nitro‐l‐arginine methyl ester (l‐NAME, 12 mm, 15 min) on the histamine‐induced airway obstruction of ovalbumin‐sensitized guinea‐pigs before, and at 5.5 h and 23.5 h after allergen challenge.
- Before allergen challenge, inhaled l‐NAME caused a significant 2.02±0.25 fold increase (P<0.01) in airway reactivity to histamine; this effect was reversed within 2.5 to 6 h after administration.
- After the allergen‐induced early asthmatic reaction at 5 h after ovalbumin provocation, a significant 3.73±0.67 fold increase (P<0.01) of the airway reactivity to histamine was observed; subsequent inhalation of l‐NAME at 5.5 h had no effect on the airway hyperreactivity, reassessed at 6 h.
- After the late asthmatic reaction, at 23 h after ovalbumin provocation, a reduced, but still significant airway hyperreactivity to histamine (2.18±0.40 fold; P<0.05) was observed. Subsequent inhalation of l‐NAME now significantly potentiated the partially reduced airway hyperreactivity 1.57±0.19 fold (P<0.05) to the level observed after the early asthmatic reaction.
- When administered 30 min before allergen exposure, l‐NAME significantly enhanced the allergen‐induced early asthmatic reaction. However, when administered at 5.5 h after allergen provocation, l‐NAME did not affect the subsequent late asthmatic reaction.
- These results indicate that endogenous NO is involved the regulation of histamine‐ and allergen‐induced bronchoconstriction and that a deficiency of cNOS‐derived NO contributes to the allergen‐induced airway hyperreactivity to histamine after the early asthmatic reaction, while a recovery of NO deficiency may account for the partial reversal of the allergen‐induced airway hyperreactivity after the late asthmatic reaction.
British Journal of Pharmacology (1998) 123, 1450–1456; doi:10.1038/sj.bjp.0701738
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